First-Line Antibiotic for Acute Bacterial Sinusitis in Adults

For an otherwise healthy adult with acute bacterial sinusitis, amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the preferred first-line antibiotic, providing 90–92% predicted clinical efficacy against the major pathogens. 1

Confirming the Diagnosis Before Prescribing

Before initiating antibiotics, confirm that the patient meets at least one of three diagnostic patterns for acute bacterial rhinosinusitis (ABRS):

Persistent symptoms ≥ 10 days with purulent nasal discharge plus either nasal obstruction or facial pain/pressure/fullness. 1
Severe symptoms ≥ 3–4 consecutive days with fever ≥ 39°C, purulent nasal discharge, and facial pain. 1
"Double sickening": initial improvement from a viral upper respiratory infection followed by worsening within 10 days. 1

Critical context: Approximately 98–99.5% of acute rhinosinusitis cases are viral and resolve spontaneously within 7–10 days without antibiotics. 1 Do not prescribe antibiotics for symptoms lasting < 10 days unless the severe criteria above are met. 1

First-Line Regimen for Otherwise Healthy Adults

Amoxicillin-clavulanate 875 mg/125 mg orally twice daily for 5–10 days (or until symptom-free for 7 consecutive days, typically 10–14 days total) is the guideline-recommended first-line agent. 1 This regimen achieves 90–92% predicted clinical efficacy against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1 The clavulanate component is essential because 30–40% of H. influenzae and 90–100% of M. catarrhalis produce β-lactamase. 1

Recent evidence supports shorter courses: 5–7 day regimens provide comparable clinical cure rates (74–80%) with fewer adverse effects compared to traditional 10-day courses. 1, 2 A meta-analysis of 12 randomized controlled trials involving 4,430 patients found no difference in clinical success between short-course (3–7 days) and long-course (6–10 days) therapy. 2

High-Dose Regimen for Risk Factors

Use high-dose amoxicillin-clavulanate 2 g/125 mg twice daily when any of the following risk factors for resistant organisms are present:

Recent antibiotic use (within the past 4–6 weeks). 1
Age > 65 years. 1
Daycare attendance or close contact with daycare children. 1
Moderate-to-severe symptoms. 1
Comorbidities (diabetes, chronic cardiac/hepatic/renal disease). 1
Immunocompromised state. 1

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Penicillin Allergy

For patients with a mild, delayed-type reaction (e.g., rash without anaphylaxis, urticaria, or angioedema):

Second- or third-generation cephalosporins for 10 days are appropriate because cross-reactivity with penicillins is negligible (< 1%). 1, 3
- Options include cefuroxime-axetil, cefpodoxime-proxetil, cefdinir, or cefprozil. 1, 3
- Cefpodoxime 200 mg twice daily for 10 days is a commonly used regimen. 3

Severe (Type I/Anaphylactic) Penicillin Allergy

For patients with a documented severe, IgE-mediated reaction (anaphylaxis, urticaria, angioedema):

Respiratory fluoroquinolones are the preferred first-line agents, providing 90–92% predicted efficacy against multidrug-resistant S. pneumoniae and β-lactamase-producing organisms. 1, 3
- Levofloxacin 500 mg once daily for 10–14 days. 1, 3
- Moxifloxacin 400 mg once daily for 10 days. 1, 3

Avoid cephalosporins in patients with a history of anaphylaxis to penicillin due to a 1–10% cross-reactivity risk with true IgE-mediated allergy. 3

Suboptimal Alternative When Fluoroquinolones Are Contraindicated

Doxycycline 100 mg once daily for 10 days is an acceptable but inferior option, with predicted efficacy of 77–81% and a 20–25% bacteriologic failure rate due to limited activity against H. influenzae. 1 Reserve this only when fluoroquinolones and cephalosporins are contraindicated (e.g., pregnancy, tendon disorders, QT-prolongation risk). 1

Antibiotics to Avoid

Macrolides (azithromycin, clarithromycin): Resistance rates exceed 20–25% for S. pneumoniae and H. influenzae; the American Academy of Pediatrics explicitly contraindicates azithromycin for acute bacterial sinusitis. 1
Trimethoprim-sulfamethoxazole: Resistance is approximately 50% in S. pneumoniae and 27% in H. influenzae. 1
First-generation cephalosporins (e.g., cephalexin): Inadequate coverage because approximately 50% of H. influenzae strains produce β-lactamase. 1

Essential Adjunctive Therapies (Add to All Patients)

Intranasal corticosteroids (e.g., mometasone, fluticasone, budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1
Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1
Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1

Monitoring and Reassessment

Reassess at 3–5 days: If there is no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone. 1
Reassess at 7 days: Persistent or worsening symptoms warrant confirmation of diagnosis, exclusion of complications (e.g., orbital cellulitis, meningitis, intracranial abscess), and consideration of imaging or ENT referral. 1

Expected timeline: Noticeable improvement should occur within 3–5 days of appropriate therapy, with complete resolution by 10–14 days or when the patient is symptom-free for 7 consecutive days. 1

Watchful Waiting Option

For adults with uncomplicated ABRS and reliable follow-up, initial observation without antibiotics is appropriate. 1 Initiate antibiotics only if there is no improvement by day 7 or if symptoms worsen at any time. 1 The number needed to treat (NNT) with antibiotics is 10–15 to achieve one additional cure compared with placebo, reflecting the high rate of spontaneous recovery. 1

Referral to Otolaryngology

Refer immediately if any of the following occur:

No improvement after 7 days of appropriate second-line antibiotic therapy. 1
Worsening symptoms at any point (increasing facial pain, fever, purulent drainage). 1
Suspected complications (severe headache, visual changes, periorbital swelling/erythema, proptosis, diplopia, altered mental status, cranial nerve deficits). 1
Recurrent sinusitis (≥ 3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities. 1

Common Pitfalls to Avoid

Do not prescribe antibiotics for symptoms < 10 days unless severe features (fever ≥ 39°C with purulent discharge for ≥ 3 consecutive days) are present. 1
Avoid routine imaging (X-ray or CT) for uncomplicated ABRS; up to 87% of viral upper respiratory infections show sinus abnormalities on imaging, leading to unnecessary interventions. 1
Ensure adequate treatment duration (≥ 5 days for adults) to prevent relapse. 1
Fluoroquinolones should not be used as first-line therapy in patients without documented β-lactam allergy to limit resistance development. 1
Gastrointestinal adverse effects with amoxicillin-clavulanate are common: diarrhea occurs in 40–43% of patients, with severe diarrhea in 7–8%. 1

What is the first‑line antibiotic for an otherwise healthy adult with acute bacterial sinusitis, and what alternatives are recommended for a patient with an immediate‑type penicillin allergy or risk factors for resistant organisms?

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